During April 2003, one study in ecstasy users, four case reports, three reviews, five studies in vitro or non-human animal studies, and one forensic study (not summarized) were found.

Mood, Memory and Imaging in Ecstasy Users
A team of researchers in Germany examined mood and psychological problems, cognitive function, and markers of serotonin transporter sites in matched samples of current ecstasy users (lifetime consumption of 817.1 +/- 1133 tablets), former ecstasy users (lifetime consumption of 767.87 +/- 579.04 tablets), polydrug users, and non-drug user controls (Thomasius et al. 2003). They found that current, but not former, ecstasy users had slightly but statistically significantly reduced numbers of serotonin transporter sites in mesencephalon and caudate, and that former, but not current, ecstasy users performed less well on specific measures of verbal recall. Higher scores on a measure of self-reported negative mood states and psychological problems were associated with drug use in general rather than with ecstasy use in particular. These findings suggest that changes in level of brain serotonin transporter may be reversible, and that impaired verbal recall is not associated with changes in serotonin transporter. Overall, the study points up the difficulty in separating out effects uniquely related to ecstasy use from effects relating to other factors, such as demographic variables, or use of other drugs.

Case Reports

Case reports included a case of gingivitis (inflamed gums) subsequent to oral storage of an ecstasy tablet in a 15-year old boy (Brazier et al. 2003), seizures and hyperthermia in a 19-year old woman after ingestion of 10 ecstasy tablets (Finsterer et al. 2003), a vehicular accident involving a 29-year old man (the driver) and a 26-year old man (the passenger) who had both taken ecstasy and methamphetamine (Weinbroum et al. 2003), and a series of adverse events following ecstasy use in the same London nightclub (Greene et al. 2003). Assessment of cerebral blood flow (CBF) in the 19-year old woman showed an immediate decline in CBF 29 days post-drug, and a return to near normal values 49 days post-drug, and the authors of the case series reported a relationship between blood MDMA levels and adverse event severity.

Reviews

Reviews located during this period include a comprehensive review of the physiological and subjective effects of MDMA, with a focus on effects in humans (Cole and Sumnall. 2003), a review directed at college health care providers featuring information on undergraduate ecstasy use (Walters 2003), and a review of neurobiological processes in substance abuse and dependence that briefly touches on possible mechanisms of MDMA effects and proposed treatment of ecstasy dependence (Lingford-Hughes et al. 2003).

MDMA Exposure in Neonatal and Young Rats

One study investigated the effects of a repeated-dose MDMA regimen on learning and memory in neonatal rats (Williams et al. 2003), and another study examined the effects of MDMA on anxiety in young (28 day-old) Lister Hooded rats (Bull et al. 2003). The first study found that neonatal MDMA exposure impaired performance on spatial memory tasks (Cincinnati Multiple T Water Maze (CWM), Morris Water Maze) without affecting swimming ability or neuroendocrine response to forced swim. Gender effects were also found, with MDMA exposure affecting only male rats' performance on the CWM, while MDMA exposure affected only female rats in specific sub-tests of the Morris Water Maze. The study in young ("adolescent") rats assessed anxiety after a moderately neurotoxic MDMA regimen, and found that MDMA-treated rats displayed reduced social interaction, but showed no increase in non-social anxiety. Findings from both studies contribute to a growing number of studies finding risks to prenatal or neonatal MDMA exposure. (The study in young rats also contributes to the literature on MDMA-induced changes in anxiety in rodents).

Drug Discrimination Tests in Rats: Training Drugs Matter

Rats trained to discriminate between MDMA, saline and LSD correctly identified lower doses of each training drug, and considered amphetamine as barely MDMA-like, yet they responded to higher doses of fenfluramine as if it were MDMA (Goodwin et al. 2003). The authors note that rats trained to discriminate between MDMA, saline and d-amphetamine responded to LSD as if it were MDMA (Goodwin and Baker 2000). These findings and findings from the previously reported study suggest that responses to test drugs in drug-discrimination trials may be influenced by the choice of training drugs.

MDMA Neurotoxicity: Findings in Mice and Rats

A study comparing the effects of methamphetamine with those of MDMA on glial activation in rats (Pubill et al. 2003) found that only methamphetamine activated microglia and astroglia at demonstrably neurotoxic doses. This means that doses of MDMA that reduce brain serotonin transporter may not trigger inflammatory processes, but that these doses may also fail to stimulate activity aiding tissue repair. Findings of reduced serotonin transporter sites along with lack of glial activation after MDMA may also be considered indicative of receptor internalization, and not serotonergic neurotoxicity, though other studies (e.g. Callahan et al. 2001) support the case for neurotoxicity. A study comparing the effects of reduced dietary selenium on MDMA neurotoxicity in mice and (Dark Agouti) rats found yet more evidence that processes underlying MDMA neurotoxicity are different in the two rodent species (Sanchez et al. 2003). Reduced dietary selenium increased MDMA neurotoxicity in mice, but not rats, and it did so without significantly altering changes in body temperature. Findings were considered evidence for greater oxidative stress in mice than in rats, and for differences in how mice and rats combat MDMA-related oxidative stress. This research is important both in increasing understanding of the nature of interspecies differences in MDMA neurotoxicity, and they may help us decide how best to extrapolate rodent findings to humans. Since MDMA produces dopamine neurotoxicity in mice and serotonin neurotoxicity in rats and primates, it may be reasonable to assume that findings in rat studies are more readily generalizable to humans than findings from mouse studies. A series of studies in mice (including serotonin transporter (SERT) knockout mice) detected increased expression of GABA transporter (GAT) genes in MDMA-treated "wild-type," but not in SERT knockout mice (Peng and Simantov 2003), suggesting that MDMA may reduce GABA availability indirectly through serotonin release. This study found that drugs that increase brain GABA availability reduced lethality after 65 mg/kg MDMA, but indirect action through modulating body temperature cannot be ruled out, as the authors did not report body temperature in each condition. Given that another study failed to note any changes in GAT gene expression in rats (Thiriet et al. 2002), it is not clear whether MDMA increases GAT genes in humans.